Maternal HFD and CDAHFD Exposure from Pregnancy to Lactation Differentially Affect Lipid Profiles and Behavior in Offspring Mice

Background/Objectives: Maternal nutritional status during pregnancy and lactation can influence metabolic and neurobehavioral development in offspring. However, the contribution of specific lipid alterations to these effects remains unclear. This study investigated whether maternal exposure to different high-fat diets produces distinct metabolic and neurobehavioral outcomes in offspring. Methods: Pregnant ICR mice were fed a control diet, a conventional high-fat diet (HFD), or a 50% choline-deficient, amino acid-defined high-fat diet (50% CDAHFD) from embryonic day 12 until weaning. Male offspring were assessed at 4–6 weeks of age for body weight, plasma lipid levels, behavioral phenotypes, prefrontal neurotransmitter release, and expression of genes related to serotonergic and dopaminergic signaling. A total of 31 dams and 196 offspring were used in the experiments and allocated to each experimental group. Results: Offspring in both HFD and 50% CDAHFD groups exhibited increased body weight and total cholesterol levels compared to controls, whereas plasma triglycerides were elevated a tendency in the 50% CDAHFD group. HFD offspring showed reduced spontaneous locomotor activity, and increased prefrontal serotonin release with altered serotonergic gene expression. Conversely, 50% CDAHFD offspring displayed increased exploratory behavior in the open field test alongside altered dopamine neuron-related genes, without locomotor or social deficits. Conclusions: Exposure of mothers to different high-fat diets has been suggested to cause specific changes in their offspring’s lipid profiles, which in turn modulate the serotonin and dopamine systems differently, leading to specific behavioral changes.